Methylphenidate appears to be the safest and most effective treatment option for attention-deficit/hyperactivity disorder in children and adolescents, while amphetamines are the preferred first-line choice in adults, a systematic review and meta-analysis have found.
Researchers reported the results of a network meta-analysis of 133 double-blind randomized controlled trials – 81 in children and adolescents, 51 in adults, and 1 in both – involving a total of 10,068 children and adolescents, and 8,131 adults. The included studies all compared a range of medications to placebo or in head-to-head trials. The meta-analysis was published online Aug. 7 in The Lancet Psychiatry.
At 12 weeks, all the medications, which included amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil, were found to be better than placebo in reducing core ADHD symptoms in children and adolescents, according to clinicians’ ratings. However, when teachers’ ratings were used, only methylphenidate and modafinil were better than placebo.
In adults, clinicians’ ratings found that amphetamines, methylphenidate, bupropion, and atomoxetine – but not modafinil – were better than placebo.
In head-to-head trials, clinicians’ ratings favored amphetamines over modafinil, atomoxetine, and methylphenidate in children, adolescents, and adults.
But in adults, amphetamines, bupropion, and methylphenidate all beat placebo.
When it came to tolerability in children and adolescents, guanfacine and amphetamines were the only two treatments that were less well tolerated than placebo. However, a post hoc analysis suggested lisdexamfetamine had a lower tolerability relative to other amphetamines, at least in children and adolescents. In adults, modafinil, amphetamines, methylphenidate, and atomoxetine were beaten by placebo for tolerability.
“Overall, all medications, except modafinil in adults, were more efficacious than placebo for the short-term treatment of ADHD, and they were less efficacious and less well tolerated in adults than in children and adolescents,” wrote Samuele Cortese, MD, PhD, of the University of Southampton (England), and his coauthors. “However, the included medications were not equivalent in relation to their mean effect size, which ranged from moderate to high and varied according to the type of rater.”
For example, while atomoxetine had the lowest mean effect size in children and adolescents based on clinicians’ ratings, in adults, it was on par with methylphenidate. Amphetamines increased diastolic blood pressure in children but not in adults.
“Taking into account both efficacy and safety, evidence from this meta-analysis supports methylphenidate in children and adolescents, and amphetamines in adults, as preferred first-choice medications for the short-term treatment of ADHD,” the authors wrote.
Dr. Cortese and his coauthors cited a few limitations. One is that the most recent study included in their meta-analysis was published in April 2017. When the researchers conducted a PubMed search in May 2018, they found three additional studies that met their criteria. “Since we already had 133 included studies, we decided that adding these three studies would not have changed the final results materially,” they wrote.
The study was supported by the Stichting Eunethydis (European Network for Hyperkinetic Disorders), and the U.K. National Institute for Health Research Oxford Health Biomedical Research Centre. Nine authors declared support, funding, or advisory roles with a range of organizations or the pharmaceutical industry.
SOURCE: Cortese S et al. Lancet Psychiatry. 2018 Aug 7. doi: 10.1016/S2215-0366(18)30269-4.